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Open Access Highly Accessed Research article

Gatekeeper of pluripotency: A common Oct4 transcriptional network operates in mouse eggs and embryonic stem cells

Maurizio Zuccotti1*, Valeria Merico2, Michele Bellone3, Francesca Mulas4, Lucia Sacchi5, Paola Rebuzzini3, Alessandro Prigione6, Carlo A Redi2, Riccardo Bellazzi45, James Adjaye6 and Silvia Garagna347*

Author affiliations

1 Sezione di Istologia ed Embriologia, Dipartimento di Medicina Sperimentale, Universita' degli Studi di Parma, Parma, Italy

2 Fondazione I.R.C.C.S. Policlinico San Matteo, Pavia, Italy

3 Laboratorio di Biologia dello Sviluppo, Dipartimento di Biologia Animale, Universita' degli Studi di Pavia, Pavia, Italy

4 Centro di Ingegneria Tissutale, Universita' degli Studi di Pavia, Pavia, Italy

5 Dipartimento di Informatica e Sistemistica, Universita' degli Studi di Pavia, Pavia, Italy

6 Molecular Embryology and Aging Group, Department of Vertebrate Genomics. Max-Planck Institute for Molecular Genetics, Berlin, Germany

7 Centro di Eccellenza in Biologia Applicata, Universita' degli Studi di Pavia, Pavia, Italy

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Citation and License

BMC Genomics 2011, 12:345  doi:10.1186/1471-2164-12-345

Published: 5 July 2011

Abstract

Background

Oct4 is a key factor of an expanded transcriptional network (Oct4-TN) that governs pluripotency and self-renewal in embryonic stem cells (ESCs) and in the inner cell mass from which ESCs are derived. A pending question is whether the establishment of the Oct4-TN initiates during oogenesis or after fertilisation. To this regard, recent evidence has shown that Oct4 controls a poorly known Oct4-TN central to the acquisition of the mouse egg developmental competence. The aim of this study was to investigate the identity and extension of this maternal Oct4-TN, as much as whether its presence is circumscribed to the egg or maintained beyond fertilisation.

Results

By comparing the genome-wide transcriptional profile of developmentally competent eggs that express the OCT4 protein to that of developmentally incompetent eggs in which OCT4 is down-regulated, we unveiled a maternal Oct4-TN of 182 genes. Eighty of these transcripts escape post-fertilisation degradation and represent the maternal Oct4-TN inheritance that is passed on to the 2-cell embryo. Most of these 80 genes are expressed in cancer cells and 37 are notable companions of the Oct4 transcriptome in ESCs.

Conclusions

These results provide, for the first time, a developmental link between eggs, early preimplantation embryos and ESCs, indicating that the molecular signature that characterises the ESCs identity is rooted in oogenesis. Also, they contribute a useful resource to further study the mechanisms of Oct4 function and regulation during the maternal-to-embryo transition and to explore the link between the regulation of pluripotency and the acquisition of de-differentiation in cancer cells.